Some of the major activities of the General Clinical Research Center may be summarized as follows: Dr. Curtis Morris has demonstrated that renal tubular acidosis can be separated into two functional subtypes which require different treatments. In one type the renal acidification defect involves a limitation of rate at which hydrogen ion can be secreted by the renal tubule cell ("rate" RTA). In the other type the renal acidification defect involves an inability of the renal tubule cell to generate normally steep lumen-peritubular hydrogen ion gradients ("gradient" RTA). Both defects result in the biochemical triad usually considered diagnostic of RTA: hyperchloremic acidosis, minimal or no azotemia, and inappropriately alkaline urine. Both give rise to rickets and abnormalities of neuromuscular function. In patients with "rate" RTA the amount of alkali therapy required to maintain correction of acidosis is several times that required in patients with "gradient" RTA. Dr. Wallace Epstein has found the concentration of free L- polypeptide chains of human immunoglobulins to be markedly elevated in the serum and urine of each of 14 azotemic patients. In two instances the concentration "L-chain" declined immediately with institution of immunosuppressive therapy prior to homotransplantation. Following successful homotransplantation, serum levels became less than 0.02 mg/ml as "L-chain" diuresis occurred. Immediate failure of graft function was characterized by continued elevation of serum and urine concentrations of "L-chain" in a pattern similar to the prenephrectomy stage. Such measurements provide both an additional index of renal function and a prognostic and diagnostic guide in the course of renal homotransplantation.